It is the objective of this project to examine the effects of morphine and related narcotic drugs on synaptic transmission within the central nervous system. This will be accomplished through study of the comparative aspects of structure-function relations which contribute to the actions of morphine on the brain. The proposed investigation is unique in that it focuses on the elementary processes which underly the organization of complex neuronal activities of which the sensorimotor and somatosensory subcortical regulatory mechanisms are comprised. We will methodically and simultaneously examine the effects of narcotics on mono-, oligo- and polysynaptic inputs in discrete brain structures with well-defined neuronal inputs and outputs. The study will thus be carried out on organization and interaction of intrinsic and extrinsic synaptic pathway of motor and limbic structures which are modified by morphine. Single units, multiunits and field potentials will be recorded in sites of cholinergic, noradrenergic, dopaminergic, serotoninergic, and mixed transmission before and after acute and chronic narcotic administration. Spontaneous discharge and responses evoked by sensory and electrical stimulation will be measured. The comparative effects of morphine on neuronal events at the various sites of transmission (raphe nucleus, substantia nigra, pineal body, cochlear nucleus, lateral geniculate body, caudate nucleus, septum, ventromedial hypothalamus, and hippocampus) will be determined. This new approach to the study of central narcotic action will provide several kinds of cogent information: the acute effects of morphine and related agents on mono- oligo- and multisynaptic events, their effects on synapses at which the neurotransmitter is identifiable, and development of tolerance to the changes induced. The proposed project will therefore provide novel information about the neurophysiologic bases of acute and chronic actions of morphine and related narcotic drugs. The undersigned agrees to accept responsibility for the scientific and technical conduct of the project and for provision of required progress reports if a grant is awarded as the result of this application.